Cross-Linked Micelles with Enzyme-Like Active Sites for Biomimetic Hydrolysis of Activated Esters
Cross-Linked Micelles with Enzyme-Like Active Sites for Biomimetic Hydrolysis of Activated Esters
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DOI：
10.1002/hlca.201700147
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发表时间：
2017-08-01
影响因子：
1.8
通讯作者：
Zhao, Yan
中科院分区：
文献类型：
--
作者：
Hu, Lan;Zhao, Yan
酶具有底物定制的活性位点，具有优化的分子识别和催化特征。尽管化学家已经使用许多不同的平台来构建酶模拟物，但系统地调整其活性位点的结构是具有挑战性的。通过在双交联胶束内分子印迹模板分子，我们创建了具有催化功能化结合位点的蛋白质大小的纳米颗粒。这些酶模拟物在背景反应中加速了活化酯的水解数千倍，而类似的催化基团（亲核吡啶衍生物）在相同条件下在本体溶液中完全无活性。模板分子直接控制活性中心的大小和形状，并调节所得催化剂在不同pH下的性能。合成的催化剂显示Michaelis-Menten酶的行为，有趣的是，逆转了固有的活性酯在水解过程中的反应性。
Enzymes have substrate-tailored active sites with optimized molecular recognition and catalytic features. Although many different platforms have been used by chemists to construct enzyme mimics, it is challenging to tune the structure of their active sites systematically. By molecularly imprinting template molecules within doubly cross-linked micelles, we created protein-sized nanoparticles with catalytically functionalized binding sites. These enzyme mimics accelerated the hydrolysis of activated esters thousands of times over the background reaction, whereas the analogous catalytic group (a nucleophilic pyridyl derivative) was completely inactive in bulk solution under the same conditions. The template molecules directly controlled the size and shape of the active site and modulated the resulting catalyst's performance at different pHs. The synthetic catalysts displayed Michaelis-Menten enzymatic behavior and, interestingly, reversed the intrinsic reactivity of the activated esters during the hydrolysis.